Management of Hypoxic-ischemic Encephalopathy.

Abstract

Hypoxic-ischemic encephalopathy (HIE), also termed as ‘perinatal asphyxia’ is a medical condition characterized by clinical and laboratory evidence of acute or sub-acute brain injury related to perinatal hypoxic-ischemic event in the neonate. HIE is a major cause of perinatal mortality and cerebral palsy worldwide and affects 2 in 1000 neonates [1]. A much higher incidence of HIE at 1.4 % for institutional deliveries was reported from India by the National Neonatal Perinatal Database following studies conducted amongst 18 medical institutes [2]. Brain injury in HIE is predominantly caused by an acute or chronic hypoxic-ischemic event causing metabolic brain dysfunction and subsequent cell death [3]. In practical terms, there is deprivation of glucose and oxygen supply to the brain. The neurological damage in HIE is an evolving process and comprises of three phases [1, 3]. The initial phase is characterized by excitotoxicity induced cellular energy failure affecting the cellular mitochondrial energy metabolism [3]. The second phase during reperfusion and reoxygenation, that occurs within hours of the initial event is characterized by a cascade of biochemical events which involve nitric oxide synthases activation, cytotoxic free radicals formation and inflammation, initiating irreversible cellular energy failure, and thereby necrosis and apoptosis [1, 3]. Tertiary brain injury describes the long-term effect of HIE on brain development including sensitization of the immune system to inflammation and low endogenous trophical factors, effecting on oligodendrocyte maturation, myelination and repair [3]. In developed countries, the standard management for HIE in infants born >36 wk of gestational age includes moderate therapeutic cooling for 72 h and is aimed at reducing major neurodisability; it only seems to work in moderate HIE and the number needed to treat is 8 [2, 4, 5]. Facilities for therapeutic cooling are not easily available in most NICUs in developing countries. Furthermore, experimental data suggests a therapeutic window for neuroprotection from therapeutic cooling being limited to initial 6 h. Considering the limited availability of cooling centers and appropriate transport facilities, alternative methods of cooling may be useful in resource limited settings [2]. An Indian study using cloth-covered icegel-packs for therapeutic cooling in 20 neonates with HIE, reported it to be safe, effective and inexpensive [6]. A systematic review and meta-analysis identified 7 studies where alternative inexpensive methods such as frozen gel packs, servo controlled fans, water bottles with tap water, ambient temperature, Blanketrol -II were used as cooling methods with good results and may be applicable in resource-limited set-ups [2, 7]. Passive cooling although remains an option but may not achieve the appropriate therapeutic level of hypothermia as evident from a study (n=134) where 64 neonates were passively cooled during transport [8]. This calls for optimizing treatment options with pharmacological agents. Several agents have been identified in experimental studies with positive effect on brain injury after HIE. Currently some of these are in trial phase. It is also important to remember that the pharmacological agents should be cheap and easily available for routine use in resource limited set-ups. This article will highlight the neuroprotective pharmacological agents which have shown promising results in studies and may soon be available as a therapeutic option in HIE. S. P. Paul (*) :H. Abdelrhim :A. Heep Department of Neonatal Medicine, Southmead Hospital, Bristol BS10 5NB, UK e-mail: siba@doctors.org.uk